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Biomedical subjects

D B Brown

Publications and source records attributed to D B Brown.

At least 55 records · Page 3Linked to original sources
PubMed1990

Analysis of cis-acting promoter elements using microinjected synthetic oligonucleotides.

The transferrin receptor (TR) is expressed in a proliferation-dependent manner that requires transcriptional activation of its gene. Furthermore TR function is required for the DNA synthetic phase of the cell cycle. Oligonucleotides encoding promoter elements within the human transferrin receptor gene were injected into quiescent fibroblasts. The cells were then serum stimulated and the effect of the oligonucleotides on nuclear labeling with [3H]thymidine was determined. Inhibition was observed for oligonucleotides corresponding to a specific region of the promoter.

Animals↗
PubMed1989

Synthesis and antitumor activity of a series of (aminoethylpyrrolidine) platinum complexes.

A series of aminoethylpyrrolidine-platinum complexes were synthesized and partially characterized for chemical structure. The leaving groups in this series of complexes were varied in an attempt to identify cytotoxic, water-soluble aminoethylpyrrolidine-platinum complexes. The cytotoxic activity was tested in vitro against L1210 cells sensitive to cis-diamminedichloroplatinum(II) (L1210/0), L1210 cells resistant to cis-diamminedichloroplatinum(II) (L1210/DDP), and L1210 cells resistant to 1,2-diaminocyclohexane platinum (L1210/DACH). The complexes were also tested for in vivo antitumor activity against L1210/0 cells injected i.p. The results of these studies indicate that the aminoethylpyrrolidine-platinum complexes have moderate antitumor activity but are cross-resistant in L1210/DDP cells. The degree of antitumor activity was dependent on the characteristic leaving group of a given complex.

Animals↗
PubMed1989

The use of bromodeoxyuridine-immunohistochemistry to identify transplanted fetal brain tissue.

The immunohistochemical detection of the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU) is shown to be a useful and reliable method to positively identify fetal brain transplants in standard histological preparations. This technique offers several advantages over the [3H]thymidine autoradiographic method, including being much more rapid and avoiding the use of radionuclides.

Animals↗
PubMed1989

Gastric xanthelasma in hyperplastic gastric polyposis.

Hyperplastic polyps of the stomach are uncommon, while xanthelasma of the gastric mucosa has a variable reported frequency. The frequency of both lesions appear increased in association with chronic gastritis and previous gastrointestinal anastomosis. The present article consists of a case report that documents for the first time (to our knowledge) the coexistence of these two lesions in a patient with a history of erosive gastritis.

Aged↗
PubMed1988

Impact of the revision of DUI legislation in Alabama.

On May 19, 1980, a major revision in the Alabama DUI laws went into effect which gave judges greater discretion in sentencing. This revision resulted in an increase in the proportion of DUI convictions, a reduction in the number of DUI citations reduced to reckless driving, a reduction in the proportion of offenders acquitted and/or dismissed, an increase in the proportion of revocations, and an increase in court referrals to an educational program on the first offense. However, the 1980 revision was accompanied by a significant increase in the percentage of alcohol-related accidents. Consequently, the Alabama legislature revised the 1980 law on July 29, 1983, the revision taking effect immediately. The more stringent penalties in the new law apparently had a positive effect on all six alcohol-related measures cited above. Most importantly, the latest revision was accompanied by a significant decrease (2.80%) in the proportion of alcohol-related accidents.

Accidents, Traffic↗
PubMed1987

Chromatin decondensation and DNA synthesis in human sperm activated in vitro by using Xenopus laevis egg extracts.

An in vitro sperm activation system was used to study nuclear swelling-chromatin decondensation and DNA synthesis; processes that occur in vivo following fertilization. Lysolecithin-permeabilized human sperm were incubated in Xenopus laevis egg extract and examined by using phase-contrast light microscopy, electron microscopy, and autoradiography. During a 3-hour incubation, the activated sperm nuclear chromatin underwent a decondensation-recondensation cycle during which DNA was synthesized. This also occurred when egg extract was given a 3-hour preincubation before the addition of the sperm, suggesting that the factor(s) required for initiating the decondensation-recondensation cycle is associated with the sperm. Because both nuclear swelling and DNA synthesis were found to be reproducible and quantifiable, we studied the effect of various agents on the two processes, characterizing the critical component(s) in the egg extract that induces these events. EGTA was found to have no effect on the induced nuclear swelling or DNA synthesis that occurs in the activated sperm. Freezing and thawing the extract or treating the extract with aphidicolin also had no effect on subsequent nuclear swelling; however, the DNA synthesis activity was blocked. Sperm incubated in extract treated with alkaline phosphatase (AP) had both nuclear swelling and DNA synthesis blocked. However, if the sperm were pretreated with DTT, and then incubated with the AP-treated extract, only the DNA synthesis activity of the extract was blocked. When the extract was treated with serine protease inhibitors (PMSF, soybean trypsin inhibitor, or alpha-2-macroglobulin), nuclear swelling occurred; however, DNA synthesis was blocked. These data suggest that phosphoproteins are involved in one or more of the activation events and that a serine protease(s) is involved in the synthesis of DNA.

Alkaline Phosphatase↗
PubMed1986

Analysis of drug involvement in traffic fatalities in Alabama.

Toxicology studies were performed on a subset of highway fatalities in Alabama. Results of those tests were analyzed for the years 1980 through 1984. It was found that 63% of driver fatalities tested had some level of blood alcohol concentration. From a smaller subset of the fatalities, it was found that almost 17% tested positively for marijuana. More than 5% of fatalities had some level of drugs (either illicit or prescription) in their blood stream. A statistical significant association was found between diazepam (tranquilizer) and low alcohol blood concentration. Another important finding is that for Alabama, marijuana is a problem drug of young drivers.

Accidents, Traffic↗
PubMed1986

Water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes as potential antitumor agents.

A series of water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes (IDP) were synthesized and tested for chemical stability, antitumor activity, and toxicity. The results obtained suggest that these complexes are relatively stable for more than 48 h when dissolved in water or phosphate buffer. All complexes had good in vitro cytotoxicity and were not cross-resistant with cis-dichloro-diammineplatinum(II) (DDP) in a DDP-resistant cell line in vitro. When the complexes were administered as a single i.p. injection to C57BL/6 X DBA/2F1 (hereafter called B6D2F1) mice inoculated with L1210 leukemia cells, a significant increase in mean survival time was observed, but there were few long-term survivors. When the complexes were administered on Days 1, 5, and 9 after tumor inoculation, however, cure rates of 50 to 85% were obtained. The oncolytic activity of the IDP complexes against L1210 ascites appeared much greater than that of DDP. The IDP complexes also had good antitumor activity when administered i.p. on Days 1, 5, and 9 following i.p. inoculation of B16 melanoma to B6D2F1 mice. Five of the six IDP complexes had no significant nephrotoxicity (as evidenced by lack of elevated blood urea nitrogen levels). N-Benzyl-iminodiacetato(1,2-diaminocyclohexane)-platinum(II) resolved into three distinct peaks of UV-absorbing material that corresponded with three distinct peaks of platinum-containing material. The exact chemical identity of the active component of this mixture is currently under investigation. The results obtained to date, however, suggest that the N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes are good candidates for further developmental studies.

Animals↗
PubMed1985

In vitro activation of human sperm induced by amphibian egg extract.

In this paper we characterize a system for the activation of human sperm using cell-free extracts from Xenopus laevis eggs. We characterize the kinetics of sperm activation in terms of morphological and DNA synthetic parameters. We have optimized some of the components which are necessary for chromatin decondensation and present data to demonstrate that the in vitro process is efficient over a wide range of salt concentrations and amounts of supplementary reducing agents.

Animals↗
PubMed1985

Early initiation of DNA synthesis in G1 phase HeLa cells following fusion with red cell ghosts loaded with S-phase cell extracts.

A modification of polyethylene glycol-mediated cell fusion procedure has been described and standardized for red blood cell mediated microinjection of proteins into cells in suspension. Using this procedure, proteins are routinely introduced into 50% of the target cells. We have applied this microinjection procedure to introduce cytoplasmic extracts obtained from S-phase HeLa cells into HeLa cells synchronized in G1. This experiment resulted in an accelerated entry of the G1 cells into S phase as measured by the incorporation of [3H]thymidine. This technique may provide a means to identify and characterize the S-phase factors responsible for the induction of DNA synthesis.

Cell Cycle↗
PubMed1985

Ascorbato(1,2-diaminocyclohexane):platinum(II) complexes, a new series of water-soluble antitumor drugs.

Dichloro-1,2-diaminocyclohexane (DACH):platinum(II), the prototype DACH:platinum complex, had good antitumor activity, was not cross-resistant with cis-dichlorodiammineplatinum(II) (DDP), but was, unfortunately, virtually insoluble in water and was, therefore, not evaluated clinically. This paper summarizes some of the chemical and biological attributes of a series of cis-bisascorbato-DACH:platinum(II) complexes (DAP). Although the primary emphasis has been placed on the DAP complex consisting of the isomeric mixture DACH, a series of complexes using the isomers of either DACH or ascorbic acid have also been synthesized. The synthetic procedure entailed reacting the water-soluble sulfato-DACH:platinum(II) with barium ascorbate, and the water-soluble product DAP was removed from the BaSO4 precipitate by filtration. Based upon elemental analysis, all the complexes had stoichiometric composition of one DACH:one platinum and two ascorbate monoanions. High-pressure liquid chromatography of cis-bisascorbato (mixed-isomer DACH):platinum revealed a series of platinum-containing, ultraviolet-absorbing peaks. All the DAP complexes had significant in vitro cytotoxicity against L1210 leukemia cells (L1210/0) with 50%-inhibitory dose values ranging from 2 to 5 micrograms/ml. None of the complexes was cross-resistant with DDP when tested in vitro against L1210 cells 50-fold resistant to DDP (L1210/DDP). The cis-bisascorbato (mixed-isomer DACH):platinum (DAP-1) was administered i.p. to C57BL X DBA/2 F1 mice inoculated i.p. with 10(6) L1210/0 cells. When administered on Days 1, 5, and 9, the DAP-1 complex consistently produced treated:control values in excess of 200% with several long-term survivors (alive 60 days after tumor inoculation). Further, the DAP-1 complex was totally non-cross-resistant with DDP when tested in vivo against a DDP-resistant L1210 line. Toxicological investigations revealed that DAP-1 was relatively nonnephrotoxic but did cause the expected bone marrow and gastrointestinal toxicity. In summary, the DAP complexes are highly water-soluble, nonnephrotoxic platinum complexes with sufficient antitumor activity to warrant further pharmacological, biochemical, and chemical investigations.

Animals↗
PubMed1984

Transient complementation of xeroderma pigmentosum cells by microinjection of poly(A)+ RNA.

An assay has been developed in which excision repair deficiency of xeroderma pigmentosum cells is transiently complemented, as measured by unscheduled DNA synthesis, by microinjection of cytoplasmic poly(A)+ RNA derived from HeLa cells. Four different complementation groups of xeroderma pigmentosum have been assayed. Groups A and G showed complementation, whereas groups D and F did not. Survival for cells in each of the groups subsequent to microinjection was approximately equal to 75%. Approximately 10-25% of surviving cells from groups A and G were complemented, as judged by near-normal unscheduled DNA synthesis. Fractionation of cytoplasmic poly(A)+ RNA on a 15-30% nondenaturing sucrose gradient and subsequent microinjection of the individual fractions indicate that repair mRNAs that complement xeroderma pigmentosum groups A and G sediment at approximately 11 S and 12 S, respectively. This assay should be of great utility in the cloning and biochemical analysis of DNA repair genes.

Autoradiography↗
PubMed1982

Synthesis and antitumor activity of new platinum complexes.

A new type of antitumor platinum complex has been prepared and examined for antitumor activity against L1210 leukemia both in vitro and in vivo. The coordination environment of platinum in these complexes consists of three anionic chloride ions and a positively charged amine. The positive charge is introduced by monoprotonation or monoalkylation of a diamine. Platinum(IV) derivatives have been prepared for several of the complexes, and a water-soluble sulfate derivative has been prepared for one of them. Several of these complexes exhibit significant in vitro activity, and trichloro(3-aminoquinuclidinium)platinum(II) (QTP) exhibits significant in vivo activity as well. An increase in life span of approximately 40% has been observed using QTP. QTP is toxic at doses slightly in excess of effective doses.

Animals↗
PubMed1982

Relationship of plasma total bilirubin, apparent unbound bilirubin and total albumin with cerebellar glycogen and abnormal Purkinje cells in the Gunn rat.

Total plasma bilirubin, apparent unbound plasma bilirubin, cerebellar glycogen and Purkinje cells were quantified in heterozygous Gunn rats, homozygous Gunn rats and normal Wistar rats. Our results indicated that, in the Gunn rat, total bilirubin, apparent unbound bilirubin, and the bilirubin/albumin molar ratio are highly correlated with each other and with alterations in cerebellar Purkinje cells and accumulation of cerebellar glycogen. In addition, cerebella of heterozygous Gunn rats contained many abnormal Purkinje cells without intramitochondrial glycogen and cerebella of homozygous Gunn rats showed many Purkinje cells with intramitochondrial glycogen. Our results demonstrate previously unreported differences between heterozygous Gunn rats and controls. We suggest that population of Purkinje cells in the heterozygous Gunn rats may have received a cellular insult from fetal exposure to bilirubin.

Animals↗
PubMed1979

Visualization of the interphase chromosomes of Ornithogalum virens and Muntiacus muntjak.

A technique for visualizing "interphase chromosomes" was applied to nuclei of the angio-spermous plant, Ornithogalum virens (2 n = 6), and the male mammal, Muntiacus munjak (2 n = 7), in an attempt to correlate the numbers of "chromosomes" visible during interphase with the respective diploid chromosome numbers. The alterations in chromosome structure observed during G1, S, and G2 periods were comparable to those previously reported in Allium cepa and Chinese hamster (CHO line) cells [33], but for technical reasons it was only possible to make accurate counts of interphase chromosomes in the G1 nuclei of O. virens. In addition, from our observations of interphase chromosomes that were pulse-labelled with tritiated thymidine and a parallel study of premature chromosome condensation (PCC) using pulse-labelled M.muntjak cells, we conclude that, although chromatin decondensation may be required for DNA synthesis, extreme chromatin decondensation can occur in the absence of DNA synthesis. Generally a morphological description of alterations in chromatin during interphase only roughly parallels the G1, S, and G2 phases defined by autoradiography following incorporation of tritiated thymidine. We suggest that both methods are valid through different ways of describing interphase.

Animals↗